We request funds to continue our in vitro studies of the electrophysiological properties of single large neurons in layer V of the cat pericruciate neocortex. In the last decade and particularly in the last five years major advances have been made in our understanding of the ionic mechanisms of the responses of neurons in the mammalian central nervous system (CNS). Our long-term objective is to understand the mechanisms whereby neurons of the mammalian CNS transduce synaptic inputs into spike trains for transmission of information on to the next cellular relay. In these experiments we will use the slice preparation and either the single or double microelectrode voltage clamp to measure ionic currents. In addition to studying voltage- and time-dependent currents, we will examine the effects of putative neurotransmitters such as acetylcholine, excitatory amino acids and neuropeptides that, based on the studies of others, cause a transient change (modulation) in the ionic currents and therefore the transduction properties of these neurons. These studies have health and biologic significance. The large neurons of layer V of sensorimotor cortex are the major output to lower centers and the spinal cord. If we are to understand major neurological problems such as epilepsy and degenerative diseases of cortex such as amyotrophic lateral sclerosis and Alzheimer's disease we must first know the normal neurobiologic properties of neocortical neurons.